After college, Sarbanes clerked with Baltimore Judge J. Frederick Motz on the U.S. District Court for the District of Maryland.[4] Sarbanes spent his professional legal career at the law firm of Venable LLP in Baltimore from 1989 to 2006, where he was chair of health care practice from 2000 to 2006 and a member of the hiring committee from 1992 to 1996.[3]

Congressman Sarbanes has introduced H.R. 2054, the No Child Left Inside Act (NCLI). This Act seeks to both improve education in the nation’s public schools and to protect the environment by “creating a new environmental education grant program, providing teacher training for environmental education, and including environmental education as an authorized activity under the Fund for the Improvement of Education.”[5] NCLI also requires states that participate in the environmental education grant programs to develop a plan to ensure that high school graduates are environmentally literate. This legislation is supported by a “coalition of over 1200 local, regional, and national organizations representing millions of concerned citizens who are anxious to see a new commitment to environmental education.”[5]

Sarbanes sought the Democratic nomination for Maryland's 3rd congressional district after 10-term incumbent Ben Cardin gave up the seat to run for the Senate seat of John Sarbanes' father, Paul Sarbanes. The primary campaign included State Senator Paula Hollinger, former Baltimore City Health Commissioner Peter Beilenson, and former Maryland Democratic Party Treasurer Oz Bengur. Sarbanes won the nomination on September 12, 2006 with 31.9% of the vote. His Republican opponent in the general election was Annapolis marketing executive John White. However, the 3rd is a heavily Democratic district that has been in that party's hands since 1927, and few expected Sarbanes to have much difficulty in the election. Sarbanes also benefited from name recognition; his father represented the district from 1971 to 1977. On November 7, 2006, Sarbanes won the general election with 64% of the vote, while White received 34% of the vote and Libertarian Charles Curtis McPeek received 2%. He has been reelected four times with no substantive opposition.

In the 2008 election cycle, the Sarbanes campaign’s income totaled $1,012,936 and his campaign spent $799,506.[6] His top individual contributor was Veneble LLP ($38,854),[6] which is where he spent his professional legal career for 18 years (1989–2006), “represent[ing] non-profit hospitals and senior living providers in their mission to deliver high quality care to the people of Maryland.” [5] Other top contributors included Johns Hopkins University, Gordon Feinblatt et al., Chesapeake Partners Management, DLA Piper, and the Carpenters & Joiners Union.[6] The top sectors that contributed money to his campaign were Finance/Insurance/Real Estate, Lawyers & Lobbyists, Labor, and Health.[6] The top industries that contributed to Sarbanes’ campaign include: Lawyers, Real Estate, Education, and Health Professionals.[6]